Periodontal diseases are chronic inflammatory diseases inducible as a result of immunoreactions of living bodies against periodontal disease bacteria inhabited in dental plaques as biofilms formed around the teeth (see Non-Patent Literature 1). It has been well known that such periodontal diseases will induce not only the inflammation or the disruption of periodontal tissues but the absorption/destruction of bones for holding the teeth called alveolar bones, and finally cause the loss of the teeth.
Recent researches on the relationship between periodontal diseases and cardiovascular diseases point out that the former diseases possibly induce the latter diseases such as cardiac attack, cardiac infarct, and brain infarct through intravascular invasions of periodontal disease bacteria and their toxins through the gum to cause intravascular inflammation and induce the formation of thrombus (see Non-Patent Literature 2). It has been also said that toxins derived from periodontal disease bacteria may act on the liver and adipocytes, decrease the secretion of insulin to increase the blood sugar level, and result in raising the risk of diabetes-related complications. On the contrary, it has been also revealed that periodontal diseases and diabetes are closely related each other in that hyperglycemic state, for example, enhances the production of inflammatory cytokines and inflammatory mediators and promotes the disruption of periodontal tissues (see Non-Patent Literature 3).
As for the prevention and the treatment of periodontal diseases, there have been conventionally conducted, as the first choice, treatments for removing periodontal disease bacteria by plaque control and cleaning gingival sulcus and periodontal pockets. Such treatments, however, have restrictive effects on halting the progress of severe periodontal diseases. There have been also used antimicrobials for bacteriostasis and sterilization of periodontal disease bacteria, and used anti-inflammatories such as dipotassium glycyrrhizinate and tranexamic acid. Medicaments with more improved effects have been eagerly desired because the above-mentioned conventional antimicrobials and anti-inflammatories have been reported effective to treat periodontitis and gingivitis accompanied by the progress of periodontal diseases and to prevent unpleasant breath and ulorrhagia, but their effects still remain insufficient.
Patent Literature 1 discloses adenosine N1-oxide and its derivatives and related compounds, i.e., 1-N-hydroxyadenosine and 1-N-hydroxyadenosine-5′-phosphate; and also discloses that 1-N-hydroxyadenosine and 1-N-hydroxyadenosine-5′-phosphate can be used as neuromodulators due to their neuromodulatory actions. The term neuromodulatory actions as referred to in Patent Literature 1 means actions of protecting and activating neurocytes or satellite cells thereof, differentiating neurocytes, repairing the intracellular transfer system of neurocytes, repairing damaged neurocytes or satellite cells thereof, activating or inhibiting neurotransmission, and modifying actions of controlling the whole nervous system normally. Patent Literature 1 relates to a technology of the use of 1-N-hydroxyadenosine and 1-N-hydroxyadenosine-5′-phosphate as remedies for central nervous system diseases such as dementia, Alzheimer's disease, senile dementia, and dysautonomia; there exists no disclosure of the use of adenosine N1-oxide and derivatives thereof in any mouthwash composition for preventing and/or treating periodontal diseases that differ from the above-mentioned central nervous system diseases in terms of their causes, symptoms, etc.
Patent Literature 2 discloses adenosine and derivatives thereof, which can be formulated into cosmetic compositions and/or dermatological compositions based on the finding of their actions on minute skin asperity and on the stimulation of regenerating the dermis and/or the epidermis by stimulating the processes of cellular metabolism and epidermal regeneration, when used in combination with mannose or rhamnose. Accordingly, Patent Literature 2 relates to a technology on cares for the skin and/or the scalp by proliferating keratinocytes and fibroblasts with adenosine, derivatives thereof, or mixtures thereof that are used in combination with mannose or rhamnose. Patent Literature 2, however, never discloses the use of adenosine N1-oxide and derivatives thereof in any mouthwash composition for preventing and/or treating oral periodontal diseases that differ from the above-mentioned cares for the skin and/or the scalp in terms of their causes and symptoms, as well as targeted body parts.
Patent Literature 3 discloses aqueous royal jelly extracts fractionated as fractions with molecular weights of 2,000 or lower, which contain at least one member selected from compounds such as adenosine, adenosine N1-oxide, adenosine-5′-monophosphate, and adenosine-5′-monophosphate-N1-oxide; and orally ingestible osteoblast-proliferation inhibitors with any one of the above compounds. Such osteoblast-proliferation inhibitors are said, for example, to be used in preventing osteoporosis through the proliferation inhibition of a human osteoblast-like cell, i.e., MG63 (a pro-osteoblast cell), to promote the cell cycle from the proliferation cycle to the osteogenic differentiation (differentiation to osteoblast) cycle. Also, in Patent Literature 3, compounds which were confirmed to promote cell cycle from proliferation cycle to osteogenic differentiation cycle are only adenosine, adenosine-5-monophosphate, and adenosine-5′-monophosphate-N1-oxide; however, adenosine N1-oxide was not confirmed. Further, Patent Literature 3 never discloses that the adenosine N1-oxide and derivatives thereof usable in the present invention are used in mouthwash compositions for preventing and/or treating periodontal diseases.
Under these circumstances, there has been desired a medicament which effectively prevents and/or treats periodontal diseases that have been recently increasing in morbidity along with affected individuals among increasingly younger people.